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2501. Pharmacokinetics and pharmacodynamics of subcutaneously administered PYY3-36 and its analogues in vivo.
作者: Jaimini Cegla.;Joyceline Cuenco.;James Minnion.;Samar Ghourab.;Klara Hostomska.;Tricia Tan.;Stephen Bloom.
来源: Lancet. 2015年385 Suppl 1卷S28页
Obesity is an emergent epidemic associated with morbidity, mortality, and psychosocial effects. One of the key gut hormones that controls appetite is peptide tyrosine-tyrosine 3-36 (PYY3-36) whose circulating half-life is only 8 min. A long-acting analogue of PYY3-36 would therefore have great potential as an antiobesity agent. The aims of this study were to investigate the effect of various aminoacid modifications of PYY3-36 on pharmacokinetics and their ability to suppress food intake.
2502. The skin microbiome in psoriatic arthritis: methodology development and pilot data.
作者: Madhura Castelino.;Stephen Eyre.;John Moat.;Graeme Fox.;Paul Martin.;Umer Ijaz.;Christopher Quince.;Pauline Ho.;Mathew Upton.;Anne Barton.
来源: Lancet. 2015年385 Suppl 1卷S27页
Skin microbiota are likely to be important in the development of conditions such as psoriatic arthritis. Profiling the bacterial community in the psosriatic plaques will contribute to our understanding of the role of the skin microbiome in these conditions. The aim of this work was to determine the optimum study design for work on the skin microbiome with use of the MiSeq platform. The objectives were to compare data generated from two platforms for two primer pairs in a low density mock bacterial community.
2503. Identification of novel biomarkers in plasma for prediction of treatment response in patients with heart failure.
作者: Thong Huy Cao.;Paulene A Quinn.;Jatinderpal K Sandhu.;Adriaan A Voors.;Chim C Lang.;Helen M Parry.;Mohapradeep Mohan.;Donald J L Jones.;Leong Loke Ng.
来源: Lancet. 2015年385 Suppl 1卷S26页
Heart failure is a complex clinical syndrome that occurs at the end stage of heart disease. Despite advances in therapy for heart failure, improvement of clinical outcomes remains a challenge for physicians. The identification of treatment response early in the course of disease would be useful to improve management of these patients. The aim of this study was to identify novel biomarkers in plasma that could predict treatment response in patients with heart failure.
2504. Role of retinoic acid in the stability of the T-helper-type 1 lineage and implications for autoimmunity.
作者: Chrysothemis Brown.;Daria Esterhazy.;Aurelien Sarde.;Venu Pullabhatla.;Mariya London.;Matthew Arno.;Emanuele de Rinaldis.;Daniel Mucida.;Graham Lord.;Randolph Noelle.
来源: Lancet. 2015年385 Suppl 1卷S25页
CD4 T cells with features of both T-helper-type 1 (Th1) and 17 (Th17) cells have been implicated in several autoimmune diseases suggesting that plasticity among CD4 T-cell lineages is potentially pathogenic. However, the factors that regulate T-cell lineage stability are largely unknown. Retinoic acid (RA) is synthesised at sites of inflammation. We hypothesised that retinoic acid, a profound epigenetic modifier, could regulate T-cell lineage stability.
2505. The influence of school in the development of eating disorders: a record-linkage study.
作者: Helen Bould.;Bianca DeStavola.;Cecilia Magnusson.;Nadia Micali.;Henrik Dal.;Jonathan Evans.;Christina Dalman.;Glyn Lewis.
来源: Lancet. 2015年385 Suppl 1卷S24页
Clinical impression is that rates of eating disorders vary between schools; we are not aware of any previous research on this topic. We aimed to investigate whether rates of eating disorders in 16-20-year-old girls vary between upper secondary schools, and to test the hypothesis that school characteristics are associated with rates of eating disorders, even after accounting for characteristics of individual students.
2506. CD57 expression in CD8 T cells and development of cutaneous squamous cell carcinoma in renal transplant recipients: a prospective cohort study.
Cutaneous squamous cell carcinoma is the most common malignancy in renal transplant recipients and a major cause of morbidity and mortality. Various measures have been proposed to identify recipients at increased risk of developing this cancer to allow targeted intervention. CD57 expression might represent a marker of T-cell exhaustion; we hypothesised that expression could predict development of squamous cell carcinoma in renal transplant recipients, and undertook a prospective cohort study to assess its predictive value.
2507. Acute alcoholic hepatitis and cellular Th1 immune responses to alcohol dehydrogenase.
作者: Laura J Blackmore.;Jennifer M Ryan.;Xiaohong Huang.;Munther Hussain.;Evangelos Triantafyllou.;Nikhil Vergis.;Godhev Manakkat Vijay.;Charalambos G Antoniades.;Mark R Thursz.;Wayel Jassem.;Diego Vergani.;Debbie L Shawcross.;Yun Ma.
来源: Lancet. 2015年385 Suppl 1卷S22页
Alcoholic hepatitis is characterised by florid hepatic inflammation, liver failure, and death within 28 days in 35% of patients. We recently showed proliferative peripheral blood mononuclear cell (PBMC) responses to alcohol dehydrogenase (ADH) in patients with alcohol-related cirrhosis, associated with T-helper-type 1 (Th1) immunity and disease severity. We aimed to define whether ADH-specific cellular immunity is present in alcoholic hepatitis.
2508. Pleiotropic effects of statins in hypercholesterolaemia: a prospective observational study using a lipoproteomic based approach.
作者: Sanjay Bhandari.;Pankaj Gupta.;Paulene Quinn.;Jatinderpal Sandhu.;Amirmansoor Hakimi.;Donald Jones.;Leong Ng.
来源: Lancet. 2015年385 Suppl 1卷S21页
The benefit of statins in the prevention of cardiovascular disease is well founded, derived from their lipid lowering and pleiotropic effects. The concept of lipoproteins as lipid transporters has evolved to encompass functions in coagulation, inflammation, and redox reactions due to their unique protein cargo. The aim of this study was to determine the effect of statin therapy on lipoproteins and their protein cargo by use of an unbiased bottom-up proteomics approach in people with hypercholesterolaemia.
2509. Effect of anandamide on endometrial adenocarcinoma (Ishikawa) cell numbers: implications for endometrial cancer therapy.
作者: Thangesweran Ayakannu.;Anthony Taylor.;Jonathon Willets.;Timothy Marczylo.;Laurence Brown.;Quentin Davies.;Esther Moss.;Justin Konje.
来源: Lancet. 2015年385 Suppl 1卷S20页
We have previously shown that patients with endometrial carcinoma express elevated concentrations of the endocannabinoid, anandamide (AEA), in both their plasma and their endometrial tissue and that the endometrial carcinoma cell line, Ishikawa, contains the receptors to which AEA binds. Several studies have reported that human and rodent cancer cell lines die in response to high AEA concentrations. The incidence of endometrial carcinoma continues to escalate and, although surgical treatment has improved, morbidity and mortality rates have not. A move towards a novel non-surgical therapeutic option is thus required, and the endocannabinoid system provides a good candidate target. We aimed to investigate the effects of AEA on the survival and proliferation of an endometrial carcinoma cell model.
2510. Effect of platelet-rich plasma on healing tissues in acute ruptured Achilles tendon: a human immunohistochemistry study.
作者: Joseph Alsousou.;Mark Thompson.;Paul Harrison.;Keith Willett.;Sarah Franklin.
来源: Lancet. 2015年385 Suppl 1卷S19页
Platelet-rich plasma (PRP), an autologous derivative of whole blood that contains a supraphysiological concentration of platelets, is thought to invoke an earlier and improved tissue healing response. This notion has been supported by in-vitro and animal studies in bone, cartilage, tendon, and muscle. To our knowledge no published study exists of the effects of PRP in human tissues in vivo. The aim of our study was to investigate the response of ruptured Achilles tendon treated with PRP.
2511. Recipient natural killer cell allorecognition of passenger donor lymphocytes and its effect on adaptive alloimmunity after transplantation.
作者: Jason Ali.;Ines Harper.;Eleanor Bolton.;J Andrew Bradley.;Gavin Pettigrew.
来源: Lancet. 2015年385 Suppl 1卷S18页
Memory T cells are known to reside in peripheral non-lymphoid tissue, but how their presence within solid organ allografts affects transplant outcomes is not known. We have previously described how graft-versus-host (GVH) allorecognition by passenger CD4 T cells within MHC class II-mismatched bm12 heart grafts provokes antinuclear humoral autoimmunity in C57BL/6 recipient mice. Here we aimed to examine how such GVH recognition affects the alloresponse to allografts with greater mismatching.
2512. Targeting indirect pathway CD4 T-cell alloresponses in the prevention of chronic transplant rejection.
作者: Jason Ali.;Eleanor Bolton.;Kourosh Saeb-Parsy.;J Andrew Bradley.;Gavin Pettigrew.
来源: Lancet. 2015年385 Suppl 1卷S17页
Uniquely, alloantigen is recognised by two pathways: as intact antigen on the surface of donor antigen-presenting cells (direct) and as self-restricted processed allopeptide (indirect). The indirect pathway is believed to be longlasting, and is generally considered to be a single entity. Here we address how indirect responses against different alloantigens differ in their strength and longevity, and how this knowledge could be used to direct immunoregulatory therapy with antigen-specific regulatory T cells (Tregs).
2513. Effect of insulin on AKR1C3 expression in female adipose tissue: in-vivo and in-vitro study of adipose androgen generation in polycystic ovary syndrome.
作者: Michael O'Reilly.;Laura Gathercole.;Farfia Capper.;Wiebke Arlt.;Jeremy Tomlinson.
来源: Lancet. 2015年385 Suppl 1卷S16页
Insulin resistance and hyperandrogenism are the cardinal features of polycystic ovary syndrome (PCOS). Women with insulin receptor (INSR) mutations develop severe hyperandrogenism secondary to hyperinsulinaemia. We hypothesised that insulin might drive adipose testosterone generation from androstenedione through aldoketoredutase type 3 (AKR1C3) in women with insulin resistance. Here we assessed the effect of insulin on AKR1C3 activity in vivo and in vitro.
2514. The role of TP53 in miRNA loading onto AGO2 and in remodelling the miRNA-mRNA interaction network.
作者: Jonathan Krell.;Justin Stebbing.;Adam Enver Frampton.;Claudia Carissimi.;Victoria Harding.;Alexander De Giorgio.;Valerio Fulci.;Giuseppe Macino.;Teresa Colombo.;Leandro Castellano.
来源: Lancet. 2015年385 Suppl 1卷S15页
DNA damage transactivates tumour protein p53 (TP53)-regulated surveillance, crucial in suppressing tumorigenesis. TP53 mediates this process directly by transcriptionally modulating gene and microRNA (miRNA) expression and indirectly by regulating miRNA biogenesis. However, the role of TP53 in regulating miRNA-AGO2 loading and global changes in AGO2 binding to its gene targets in response to DNA damage are unknown. These processes might be novel mechanisms by which TP53 regulates miRNAs in response to DNA damage.
2515. Retinal development in albinism: a prospective study using optical coherence tomography in infants and young children.
作者: Helena Lee.;Ravi Purohit.;Viral Sheth.;Eleni Papageorgiou.;Gail Maconachie.;Rebecca J McLean.;Aarti Patel.;Anastasia Pilat.;Samira Anwar.;Nagini Sarvanathan.;Frank A Proudlock.;Irene Gottlob.
来源: Lancet. 2015年385 Suppl 1卷S14页
Retinal development normally involves migration of the inner retinal layers away from the fovea, migration of the cone photoreceptors into the fovea, and elongation of the photoreceptors over time. This process is arrested prematurely in albinism. However, because retinal development continues at least until the age of 4 years, when development arrests in albinism is uncertain. In this study we outlined the time course of retinal development in children with albinism.
2516. Genetic variants associated with non-typhoidal Salmonella bacteraemia in African children.
作者: James J Gilchrist.;Tara C Mills.;Vivek Naranbhai.;Stephen J Chapman.;Benjamin P Fairfax.;Julian C Knight.;Thomas N Williams.;J Anthony G Scott.;Calman A MacLennan.;Anna Rautanen.;Adrian V Hill.; .
来源: Lancet. 2015年385 Suppl 1卷Suppl 1期S13页
Non-typhoidal Salmonella (NTS) causes invasive and frequently fatal disease in African children. Existing strategies to prevent, diagnose, and treat NTS disease are inadequate. An improved understanding of the biology of invasive Salmonella infection will facilitate the development of novel NTS control measures. Despite evidence in mice and man showing a clear role for host genetics in NTS susceptibility, there are no published studies investigating host genetic susceptibility to NTS in African populations.
2517. Role of melanocortin signalling in the preference for dietary macronutrients in human beings.
作者: Agatha van der Klaauw.;Julia Keogh.;Elana Henning.;Cheryl Stephenson.;Victoria M Trowse.;Paul Fletcher.;Sadaf Farooqi.
来源: Lancet. 2015年385 Suppl 1卷Suppl 1期S12页
Signalling though the melanocortin 4 receptor (MC4R), which is widely expressed in the hypothalamus, mediates food intake and macronutrient preference in rodents. Studies in patients with MC4R deficiency can provide insights into the role of this pathway in man. We investigated the role of melanocortin signalling in fat and sucrose preference in human beings by studying patients with loss of function mutations in MC4R.
2518. Revascularisation of renal artery stenosis as a therapy for heart failure: an observational cohort study.
作者: Darren Green.;James P Ritchie.;Constantina Chrysochou.;Philip A Kalra.
来源: Lancet. 2015年385 Suppl 1卷S11页
Heart failure contributes to 5% of all hospital admissions, and mortality is more than 50% at 4 years. 54% of patients with a left ventricular ejection fraction of less than 40% have renal artery stenosis. The potential benefit of revascularisation for heart failure is not established. We aimed to compare clinical outcomes for renal artery revascularisation with medical therapy for renal artery stenosis associated with heart failure as the first step towards validating revascularisation as a therapeutic option in heart failure.
2519. Microvascular and endothelial function for risk prediction in dengue: an observational study.
作者: Sophie Yacoub.;Heiman Wertheim.;Cameron P Simmons.;Gavin Screaton.;Bridget Wills.
来源: Lancet. 2015年385 Suppl 1卷S102页
Dengue infection can result in a wide spectrum of disease. The defining feature of severe disease is increased capillary permeability, which can lead to hypovolaemic shock. Microvascular and endothelial dysfunction might underlie hypovolaemic shock, but they have not been assessed clinically. We aimed to investigate the use of microvascular assessment as a prognostic method in dengue.
2520. Tumour metabolism in squamous cell carcinoma of the head and neck: an in-vitro study of the consequences of TP53 mutation and therapeutic implications.
作者: Mark Wilkie.;Andrew Lau.;Nikolina Vlatkovic.;Terence Jones.;Mark Boyd.
来源: Lancet. 2015年385 Suppl 1卷S101页
Survival for squamous cell carcinoma of the head and neck (SCCHN) has not improved substantially in recent years. Since radiotherapy is a cornerstone of treatment, it is crucial to identify ways to augment its efficacy, for which tumour metabolism is an attractive target. p53 is a metabolic mediator, and TP53 mutations are common in this disorder. We sought to investigate metabolic changes in SCCHN, to elucidate any correlation with TP53 status, and to determine whether targeted metabolic therapy might be used to potentiate the effects of radiation.
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